Biochip manufacturing method and biochip manufacturing device

ABSTRACT

Provided is a method of manufacturing a biochip using a droplet discharging device including a droplet discharging head having a cavity and a nozzle hole provided in communication with the cavity, and a liquid housing unit connected to the cavity via a passage, having the steps of filling a retention liquid which separates without getting mixed with the sample liquid into the liquid housing unit, the passage, and the cavity; injecting the sample liquid into the liquid housing unit; moving the sample liquid from the liquid housing unit to the cavity by discharging the retention liquid from the nozzle hole; stopping the discharge of the retention liquid at the moving step upon detecting with a sensor that the sample liquid reached a position adjacent to the nozzle hole; and delivering the sample liquid as droplets onto the object by discharging the sample liquid from the nozzle hole.

CROSS-REFERENCES

This application is a divisional of U.S. patent application Ser. No.11/497,736 filed on Aug. 2, 2006. This application claims the benefit ofJapanese Patent Application No. 2005-248756 filed on Aug. 30, 2005. Thedisclosures of the above applications are incorporated herein byreference.

BACKGROUND

1. Technical Field

The present invention pertains to improved technology in the case ofusing a droplet discharging device for the manufacture of a so-calledbiochip in which a biological material is immobilized on an object suchas a substrate.

2. Related Art

In recent years, so-called biochips (microarrays) formed by immobilizinga biological material such as DNA (nucleic acid), protein or antibody asthe probe onto a substrate (chip) is attracting keen attention.Conventionally, biochips were manufactured by attaching a sample liquidcontaining DNA to the tip of a pin with a solid pin spotter, andtranscribing this onto a chip. Nevertheless, this method hadinconveniences such as contamination due to the contact with thespotter, low productivity and so on. Thus, the use of a dropletdischarging device for manufacturing biochips in a non-contact andhighly efficient manner is being considered.

Generally, biological materials such as nucleic acid used as the probeare often extremely expensive, and the obtained amount (absolute amount)for use in medical diagnosis and so on is usually small. Thus, whenusing a droplet discharging device for manufacturing a biochip, there isa technical task of avoiding as much as possible the waste of the sampleliquid containing the biological material. In order to achieve theforegoing task, JP-A-2004-160368 discloses a small cartridge capable ofstably retaining a sample liquid, even in small amounts, by using abundle of a plurality of capillary tubes as the tank for storing theliquid containing the biological material.

Nevertheless, in the case of a droplet discharging head, when fillingthe sample liquid from the cartridge to the head through minute flowchannels, there are inherent problems in that small amounts of wastefluid will arise due to the discharge of air bubbles, and residualliquid that could not be discharged will remain in the head even afterthe discharge. Thus, the foregoing problems could not be completelyresolved even with the miniaturization of the cartridge as describedabove, and there is still room for improvement. Specifically, whenfilling the sample liquid in the droplet discharging head, a method ofsucking the sample liquid from the nozzle hole (discharge opening) ofthe droplet discharging head with a suction pump is adopted. Here, evenassuming that it is possible to stop the suction operation at theinstant the sample liquid reaches the nozzle hole, since it is difficultto instantaneously eliminate the inertia of the sample liquid or thenegative pressure of the suction pump, the sample liquid will continueto be discharged from the nozzle hole for a while after the suctionoperation is stopped. More realistically, air bubbles are engulfed inthe sample liquid due to the sudden aspect change between the minuteflow channels and the cavity (liquid housing chamber) in the dropletdischarging head connected to such minute flow channels, and these airbubbles cause a defective discharge. Thus, in order to completelydischarge the air bubbles, the suction operation is continued for awhile after the sample liquid reaches the nozzle hole. Therefore, thecurrent status is that large amounts of sample liquid are wasted aswaste liquid.

SUMMARY

Accordingly, an advantage of some aspects of the invention is to providemanufacturing technology enabling the manufacture of biochips byavoiding as much as possible the waste of the sample liquid.

According to a first aspect of the invention, provided is a method ofmanufacturing a biochip using a droplet discharging device including adroplet discharging head having a cavity and a nozzle hole provided incommunication with the cavity, and a liquid housing unit connected tothe cavity via a flow channel, that delivers in drops a sample liquidcontaining a biological material onto a prescribed object from thenozzle hole of the droplet discharging head. This biochip manufacturingmethod includes the steps of filling a retention liquid that has roughlythe same specific gravity as the sample liquid and which separateswithout getting mixed with the sample liquid into the liquid housingunit, the flow channel, and the cavity; injecting the sample liquid intothe liquid housing unit; moving the sample liquid from the liquidhousing unit to the cavity by discharging the retention liquid from thenozzle hole of the droplet discharging head; stopping the discharge ofthe retention liquid at the moving step upon detecting with a sensorthat the sample liquid reached a position adjacent to the nozzle hole ofthe cavity; and delivering the sample liquid as droplets onto the objectby disposing the droplet discharging head above the object anddischarging the sample liquid from the nozzle hole.

According to a second aspect of the invention, provided is a method ofmanufacturing a biochip using a droplet discharging device including adroplet discharging head having a cavity and a nozzle hole provided incommunication with the cavity, and a liquid housing unit connected tothe cavity via a flow channel, that delivers in drops a sample liquidcontaining a biological material onto a prescribed object from thenozzle hole of the droplet discharging head. This biochip manufacturingmethod includes the steps of filling a retention liquid that has roughlythe same specific gravity as the sample liquid and which separateswithout getting mixed with the sample liquid into the liquid housingunit, the flow channel, and the cavity; injecting the sample liquid intothe liquid housing unit; moving the sample liquid from the liquidhousing unit to the cavity by discharging the retention liquid from thenozzle hole of the droplet discharging head; stopping the discharge ofthe retention liquid at the moving step when the retention liquid isdischarged in an amount that is roughly equal to the amount filled atthe filling step; stopping the discharge operation of the dropletdischarging head upon operating the droplet discharging head anddetecting with a sensor that the liquid discharged from the nozzle holechanged from the retention liquid to the sample liquid; and deliveringthe sample liquid as droplets onto the object by disposing the dropletdischarging head above the object and discharging the sample liquid fromthe nozzle hole.

According to the manufacturing method of the foregoing aspects, it ispossible to replace the waste liquid, which is discharged until thesample liquid is sufficiently filled in the cavity, with a retentionliquid by suitably selecting an inexpensive retention liquid. Therefore,it is possible to manufacture biochips by avoiding as much as possiblethe waste of the expensive and scarce sample liquid.

Further, the preferred conditions for the foregoing aspects in theinvention are explained below.

Preferably, the sample liquid is a liquid with water as the solvent, andthe retention liquid is an oily liquid. Contrarily, the sample liquidmay be a liquid with oil as the solvent, and the retention liquid may bean aqueous liquid.

According to the above, it is possible to easily realize the combinationof a sample liquid and a retention solution that get separated withoutgetting mixed together.

Further, when the sample liquid contains a fluorescent material, thesensor may detect the fluorescence emitted by the fluorescent material.

When a fluorescent material is contained in the sample liquid to be usedfor manufacturing biochips, it is possible to easily detect theswitching from the retention liquid to the sample liquid by using suchfluorescent material.

Further, the sensor may include a pair of electrodes provided near thenozzle hole of the droplet discharging head, and detect the dielectricconstant of the sample liquid or the retention liquid interposed betweenthe electrodes.

Thereby, even if the sample liquid does not contain a fluorescentmaterial, it is still possible to detect the switching from theretention liquid to the sample liquid.

According to a third aspect of the invention, provides is a device thatmanufactures a biochip by delivering in drops a sample liquid containinga biological material onto a prescribed object. This biochipmanufacturing device includes a droplet discharging head having a cavityand a nozzle hole provided in communication with the cavity, and whichdischarges liquid from the nozzle hole according to a drive signal; aliquid housing unit connected to the cavity via a flow channel and whichhouses the sample liquid and a retention liquid that has roughly thesame specific gravity as the sample liquid and which separates withoutgetting mixed with the sample liquid; a table that supports the object;a drive unit that relatively moves the droplet discharging head and thetable; and a sensor that detects that the sample liquid reached aposition adjacent to the nozzle hole of the cavity.

According to the foregoing configuration, it is possible to replace thewaste liquid, which is discharged until the sample liquid issufficiently filled in the cavity, with a retention liquid by suitablyselecting an inexpensive retention liquid. Therefore, it is possible tomanufacture biochips by avoiding as much as possible the waste of theexpensive and scarce sample liquid.

Preferably, the sensor detects the fluorescence emitted from afluorescent material mixed into the sample liquid.

Since a fluorescent material is often contained in the sample liquidused for manufacturing biochips, it is possible to easily detect theswitching from the retention liquid to the sample liquid by using suchfluorescent material.

Further, the sensor may include a pair of electrodes provided near thenozzle hole of the droplet discharging head, and detect the dielectricconstant of the sample liquid or the retention liquid interposed betweenthe electrodes.

Thereby, even if the sample liquid does not contain a fluorescentmaterial, it is still possible to detect the switching from theretention liquid to the sample liquid.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic perspective view explaining the configuration ofthe biochip manufacturing device;

FIG. 2A and FIG. 2B are diagrams explaining the detailed configurationof the droplet discharging head;

FIG. 3A to FIG. 3C are diagrams explaining the manufacturing method of abiochip;

FIG. 4A to FIG. 4C are diagrams explaining the manufacturing method of abiochip;

FIG. 5A and FIG. 5B are diagrams explaining another configurationexample of a fluorescent sensor; and

FIG. 6 is a diagram explaining another configuration example of asensor.

DESCRIPTION OF EXEMPLARY EMBODIMENTS

Embodiments of the present invention are now explained with reference tothe attached drawings.

FIG. 1 is a schematic perspective view explaining the configuration ofthe biochip manufacturing device according to an embodiment of thepresent invention. The biochip manufacturing device 1 shown in FIG. 1 isused for manufacturing biochips by forming the sample liquid containinga biological material into droplets, and delivering such droplets onto achip (object) 100 formed from a glass substrate. As shown in FIG. 1, thebiochip manufacturing device 1 of this embodiment is configured byprimarily including a droplet discharging head 10, a sample cartridge(liquid housing unit) 18, an aspiration unit 20, a fluorescent sensor22, a flow channel plate 24, a table 26, a fixation unit 28, aZ-direction drive unit 30, an X-direction drive unit 32, and aY-direction drive unit 34.

The droplet discharging head 10 discharges as droplets the liquidsupplied from the sample cartridge according to a drive signal providedfrom a control unit not shown. Incidentally, the detailed configurationof the droplet discharging head 10 will be described later.

The sample cartridge 18 is connected to the droplet discharging head 10via the flow channel plate 24, and houses the liquid to be discharged tothe droplet discharging head 10 as the discharge target. According tothis embodiment, the sample cartridge 18 houses the sample liquid and aretention liquid that has roughly the same specific gravity as thesample liquid and which separates without getting mixed with the sampleliquid. Incidentally, the relationship of the sample liquid and theretention liquid will be described later.

The aspiration unit 20 is provided at the corner of the table 26, and isused for filling the liquid as the discharge target in the dropletdischarging head 10. Specifically, the droplet discharging head 10 isdisposed such that the nozzle hole forming face comes in contact withthe suction cap of the aspiration unit 20, and, by operating the suctionpump (not shown) connected to the suction cap, the liquid inside thedroplet discharging head 10 is sucked and discharged. Further, theaspiration unit 20 also has the function of receiving the dischargedliquid (waste liquid).

The fluorescent sensor 22 is configured by including a CCD camera andthe like, and is used for detecting that the sample liquid reached thevicinity of the nozzle hole of the droplet discharging head 10.Specifically, the sample liquid of this embodiment contains afluorescent material, and the fluorescent sensor 22 detects that thesample liquid reached the vicinity of the nozzle hole by observing thefluorescence emitted from the fluorescent material near the nozzle hole.Incidentally, details regarding the detection operation of thefluorescent sensor 22 will be described later.

The flow channel plate 24 is a tabular member having a groove or athrough-hole of a prescribed shape, and is used for configuring a flowchannel 16 (refer to FIG. 3 described later) interposed between thedroplet discharging head 10 and the sample cartridge 12 for passing thesample liquid and the like.

The table 26 supports a plurality of chips 100 as the object. As shownin FIG. 1, the table 26 is mounted on the Y-direction drive unit 34.

The fixation unit 28 is used for fixing the droplet discharging head 10,the sample cartridge 18 and the flow channel plate 24 on the Z-directiondrive unit 30.

The Y-direction drive unit 34 is used for freely moving the table 26 inthe Y direction shown in FIG. 1. Similarly, the X-direction drive unit32 is used for freely moving the table 26 in the X direction shown inFIG. 1. In this example, the table 26 and the Y-direction drive unit 34are mounted on the X-direction drive unit 32, and these are configuredto be movable in the X direction as a whole. Further, the Z-directiondrive unit 30 is used for freely moving the fixation unit 28 and thedroplet discharging head 10 fixed to the fixation unit 28 in the Zdirection shown in FIG. 1. A control unit not shown supplies a drivesignal to the Z-direction drive unit 30, the X-direction drive unit 32and the Y-direction drive unit 34, respectively. With the biochipmanufacturing device 1 of this embodiment, the droplet discharging head10 is moved relatively to the table 26 by appropriately operating theZ-direction drive unit 30, the X-direction drive unit 32 and theY-direction drive unit 34, and discharges an appropriate amount of thesample liquid at a suitable position on the chip 100 in order tomanufacture a biochip. In other words, in this embodiment, theZ-direction drive unit 30, the X-direction drive unit 32 and theY-direction drive unit 34 correspond to the “drive unit” of theinvention.

FIG. 2 is a diagram explaining the detailed configuration of the dropletdischarging head 10. More specifically, FIG. 2A is a perspective view ofthe droplet discharging head 10, and FIG. 2B is an exploded perspectiveview of the droplet discharging head 10. The illustrated dropletdischarging head 10 is an electrostatically driven droplet discharginghead, and is configured by affixing together a cover glass 41, acompression chamber substrate 42 and an electrode substrate 43. Thecompression chamber substrate 42 is formed so that a reception opening44 of the liquid supplied from the sample cartridge 12 via the flowchannel, the cavity (compression chamber) 12 and the nozzle hole 14 arein communication. A diaphragm is provided to a part of the wall surfaceof the cavity 12. The electrode substrate 43 has a counter electrode 45placed opposite the diaphragm of the cavity 12 by maintaining a gap of aprescribed spacing. When a potential difference is applied to thediaphragm and the counter electrode 45, the diaphragm will be subject toelastic deformation and be gravitated toward the counter electrode 45,and negative pressure will be applied to the cavity 12. Thereafter, whenthe potential difference between the diaphragm and the counter electrode45 is released, a minute amount of liquid in the cavity 12 is dischargedfrom the nozzle 14 due to the restoring force of the diaphragm.

The biochip manufacturing device 1 of this embodiment is configured asdescribed above, and the method of using this biochip manufacturingdevice 1 to manufacture a biochip by delivering in drops a sample liquidcontaining a biological material onto the chip 100 is now explained indetail.

Here, before describing this manufacturing method, the sample liquid andretention liquid used in this embodiment are explained. As describedabove, a retention liquid that has roughly the same specific gravity asthe sample liquid and which separates without getting mixed with thesample liquid is used. For example, if the sample liquid is a liquid(aqueous solution) with water as the solvent, an oily liquid can be usedas the retention liquid. As the retention liquid to be used in theforegoing case; for instance, vegetable oil in liquid form at roomtemperature is preferably used. Specifically, vegetable oil havingpalmitoleic acid, oleic acid, linoleic acid, α-linoleic acid,arachidonic acid, eicosapentaenoic acid, docosa-hexaenoic acid, inolenicacid, or the like as its primary component is preferably used. Further,if the sample liquid is a liquid with oil as the solvent, an aqueousliquid can be used as the retention liquid. As the retention liquid tobe used in the foregoing case, water or a solution containing a suitablesubstance can be used.

FIG. 3 and FIG. 4 are diagrams explaining the biochip manufacturingmethod. For the sake of convenience in explaining the invention, therespective drawings represent a simplified configuration of the dropletdischarging head 10, the sample cartridge 18 and other components.

Foremost, a retention liquid 50 is filled in the sample cartridge 18,the flow channel 16, and the cavity 12 of the droplet discharging head10 (FIG. 3A). Specifically, as described above, the droplet discharginghead 10 is disposed such that the forming face of the nozzle hole 14comes in contact with the aspiration unit 20 so as to operate thesuction pump (not shown) connected to the aspiration unit 20. Thereby,the retention liquid 50 is sucked via the nozzle hole 14 of the dropletdischarging head 10, and the retention liquid 50 housed in the samplecartridge 18 is also filled in the flow channel 16 and the cavity 12.Thereupon, the waste liquid 50 a resulting from such suction isdischarged into the aspiration unit 20.

Subsequently, a suitable amount of the sample liquid 52 is injected intothe sample cartridge 18 using a dispenser or the like (FIG. 3B). Here,the sample liquid 52 and the retention liquid 50 are maintaining amutually separated state in the sample cartridge 18. As shown indrawings, in this embodiment, the retention liquid 50 exists at theperiphery of the sample liquid 52, and since the sample liquid 52maintains a state of not coming in direct contact with the outside world(air, etc.), it is possible to inhibit the deterioration or the like ofthe sample liquid 52.

Subsequently, the sample liquid 52 is moved from the sample cartridge 18to the cavity 12 by discharging the retention liquid 50 from the nozzlehole 14 of the droplet discharging head 10 (FIG. 3C, FIG. 4A).Specifically, the droplet discharging head 10 is disposed such that theforming face of the nozzle hole 14 comes in contact with the aspirationunit 20 so as to operate the suction pump (not shown) connected to theaspiration unit 20. Thereby, the retention liquid 50 is sucked via thenozzle hole 14 of the droplet discharging head 10, and the retentionliquid 50 housed in the sample cartridge 18 passes through the flowchannel 16 and the cavity 12, and is discharged as the waste liquid 50a. Since the retention liquid 50 and the sample liquid 52 are roughly ofthe same specific gravity, together with the discharge of the retentionliquid 50, the sample liquid 52 also passes through the flow channel 16and arrives at the cavity 12 as illustrated in the drawings.

Incidentally, although the sample liquid 52 may be moved as a result ofmaking the droplet discharging head 10 performing the operation ofdischarging the retention liquid 50 in the foregoing process, theforegoing suction method is more preferable from the perspective ofshortening the time required for the process.

Further, in parallel with the foregoing process (refer to FIG. 3C, FIG.4A), the fluorescent sensor 22 is used to observe the vicinity of thenozzle hole 14 of the droplet discharging head 10. Specifically, asshown in FIG. 3C, FIG. 4A and FIG. 4B, with the droplet discharging head10 of this embodiment, it is possible to observe the vicinity of thenozzle hole 14 with the fluorescent sensor 22 through a transparentcover glass 41. When the sample liquid 52 reaches a position adjacent tothe nozzle hole 14 of the cavity 12, the fluorescence emitted from thefluorescent material contained in the sample liquid 52 is detected bythe fluorescent sensor 22, and the discharge of the retention liquid 50described above is stopped (FIG. 4B). Specifically, a detection signalfrom the fluorescent sensor 22 is input to a control unit not shown, andthe control unit stops the suction operation of the aspiration unit 20.

Subsequently, the droplet discharging head 10 is disposed above the chip100 as the object, and the sample liquid 52 is discharged from thenozzle hole 14 and delivered as drops onto the chip 100 (FIG. 4C).Thereby, it is possible to obtain a biochip in which the droplets 52 adischarged from the droplet discharging head 10 are aligned on the chip100.

FIG. 5 is a diagram explaining another configuration example of thefluorescent sensor 22. When the droplet discharging head 10 isconfigured from an opaque material and it is difficult to observe thevicinity of the nozzle hole 14, the fluorescent sensor 22 should bedisposed so that the liquid discharged from the nozzle hole 14 can beobserved as shown in the drawings. In this case, as with the foregoingembodiment, the retention liquid 50 is discharged by disposing thedroplet discharging head 10 such that it comes in contact with theaspiration unit 20 so as to operate the suction pump (not shown)connected to the aspiration unit 20. Here, the suction pump is stoppedat the point when the retention liquid 50 in an amount that is roughlyequal to the amount filled in the sample cartridge 12 (refer to FIG. 3A)is discharged so as to stop the discharge of the retention liquid 50.Subsequently, as shown in FIG. 5A and FIG. 5B, when the dropletdischarging head 10 is operated and the fluorescent sensor 22 detectsthat the droplet discharged from the nozzle hole has changed from thedroplet 50 a of the retention liquid 50 to the droplet 50 a of thesample liquid 52, the discharge operation of the droplet discharginghead 10 is stopped. Incidentally, in the illustrated example, althoughthe configuration enables the droplet discharged from the nozzle holes14 to be immediately observed with the fluorescent sensor 22, theconfiguration may also be such that the droplet is delivered andattached to a suitable location (on a dummy chip, for instance), and theattached droplet is observed with the fluorescent sensor 22.

With this embodiment described above, it is possible to replace thewaste liquid, which is discharged until the sample liquid 52 issufficiently filled in the cavity, with a retention liquid by suitablyselecting an inexpensive retention liquid 50. Therefore, it is possibleto manufacture biochips by avoiding as much as possible the waste of theexpensive and scarce sample liquid.

Incidentally, the present invention is not limited to the subject matterof the embodiments described above, and may be implemented in variousmodifications within the scope of the gist of the invention. Forinstance, in the foregoing embodiments, although a case was assumedwhere a fluorescent material is contained in the sample liquid and thefluorescent sensor 22 for detecting the fluorescence emitted from thefluorescent material was used, a sensor employing other principles mayalso be adopted.

FIG. 6 is a diagram explaining another configuration example of thesensor, and shows a partial cross section in the vicinity of the nozzlehole of the droplet discharging head 10. The sensor shown in FIG. 6 isconfigured by including a pair of electrodes 28 provided to the vicinityof the nozzle hole 14 of the droplet discharging head 10. When thesample liquid 52 or the retention liquid 50 passes through the pair ofelectrodes 28, the sample liquid 52 or the retention liquid 50 will beinterposed between the electrodes. Here, by applying a faint voltagebetween the electrodes and detecting the capacitance, it is possible todetect the dielectric constant of the sample liquid 52 or the retentionliquid 50. Since there will be a difference in the detected value of thedielectric constant due to the difference in the solvent used in thesample liquid 52 and the retention liquid 50, it is possible to detectchanges in the liquid discharged from the nozzle hole 14 of the dropletdischarging head 10 based on such difference. Incidentally, the pair ofelectrodes 28 may also be provided in the cavity 12, and not in thevicinity of the nozzle hole 14. In addition, a sensor for detecting thedifference in optical characteristics (transmission, reflectivity, etc.)of the sample liquid 52 of the retention liquid 50 can also be used. Inthis case, for instance, it would be preferable to perform treatmentsuch as mixing a suitable pigment to the retention liquid 50 in order tofurther distinguish the difference in optical characteristics of theretention liquid 50 and the sample liquid 52. Further, a method ofincluding a radioisotope such as a hydrogen isotope in the sample liquid52 or the retention liquid 50 and using a sensor to detect the radiationemitted therefrom, or a method of including a magnetic material in thesample liquid 52 or the retention liquid 50 and using a sensor to detectthe magnetic line emitted therefrom may also be adopted.

Moreover, in the foregoing embodiments, although a case was illustratedusing an electrostatically driven droplet discharging head, a dropletdischarging head of a different system (for instance, a piezo system orair bubble system) may also be adopted.

Further, in the foregoing embodiment, although the focus of attentionwas on a biochip manufacturing device and a biochip manufacturingmethod, the present invention can also be applied to the manufacture ofelectronic devices such as an organic electroluminescence device or anorganic thin film transistor by using the droplet discharging device. Inthis case, it is possible to reduce the usage of the expensive liquidmaterial used in forming the elements.

1. A device that manufactures a biochip by delivering in drops a sampleliquid containing a biological material onto a prescribed object,comprising: a droplet discharging head having a cavity and a nozzle holeprovided in communication with the cavity, and which discharges liquidfrom the nozzle hole according to a drive signal; a liquid housing unitconnected to the cavity via a flow channel and which houses the sampleliquid and a retention liquid that has roughly the same specific gravityas the sample liquid and which separates without getting mixed with thesample liquid; a table that supports the object; a drive unit thatrelatively moves the droplet discharging head and the table; and asensor that detects that the sample liquid reached a position adjacentto the nozzle hole of the cavity.
 2. The biochip manufacturing deviceaccording to claim 1, wherein the sensor detects the fluorescenceemitted from a fluorescent material mixed into the sample liquid.
 3. Thebiochip manufacturing device according to claim 1, wherein the sensorincludes a pair of electrodes provided near the nozzle hole of thedroplet discharging head, and detects the dielectric constant of thesample liquid or the retention liquid interposed between the electrodes.